The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus

Table 1

Nrf2/Keap1/ARE and diabetic complications.

Diabetic complication	Pathogenesis	Nrf2- (or downstream-) mediated effects
Atherosclerosis	(i) oxLDL formation	(i) Protection from oxLDL transformation of phagocytic cells [77, 78]
	(ii) Proinflammatory response in endothelial cells	(ii) Inhibition of proinflammatory response at atherosusceptible sites [71, 79]
Heart failure	(i) Aberrant cardiac and ECM remodeling	(i) Blood pressure regulation [72]
	(ii) Insulin resistance of myocytes	(ii) Protection of myocardium following ischemia
	(iii) Impaired regulation of intracellular calcium	(iii) Diminishes ROS and myocardial hypertrophy [99]
	(iv) Accumulation of AGE products
Diabetic nephropathy	(i) Renal oxidative and nitrosative stress	(i) Improvement of metabolic indices (e.g., polydipsia and polyuria) [110]
	(ii) Mesangial cell proliferation, inflammation, fibrosis	(ii) Reversal in dysfunction of key growth factors and ECM proteins [111–113]
Wound healing	(i) Keap1 overexpression	(i) Impairments in angiogenesis and reepithelialization [120]
	(ii) Loss of wound redox homeostasis
	(iii) Chronic inflammatory microenvironment